Hexaphenoxycyclotriphosphazene (HPCTP), an unregistered chemical, has been used as a substitute for triphenyl phosphate in flame retardants and plasticizers. Here, we identified its metabolite, pentaphenoxycyclotriphosphazene (PPCTP) in the liver of Japanese medaka exposed to HPCTP. When sexually mature female medaka were exposed to HPCTP at 37.0, 90.4, and 465.4 ng/L for 35 days, the HPCTP concentration (642.1–2531.9 ng/g lipid weight [lw]) in the embryos considerably exceeded that (34.7–298.1 ng/g lw) in the maternal muscle, indicating remarkable maternal transfer. During 0–9 days postfertilization, the HPCTP concentration in the embryos decreased continuously, while the PPCTP concentration increased. HPCTP and PPCTP antagonized the retinoic X receptor with 50% inhibitory concentrations (IC₅₀) of 34.8 and 21.2 μM, respectively, and PPCTP also antagonized the retinoic acid receptor with IC₅₀ of 2.79 μM. Such antagonistic activities may contribute to eye deformity (4.7% at 465.4 ng/L), body malformation (2.1% at 90.4 ng/L and 6.8% at 465.4 ng/L), and early developmental mortality (11.6–21.7% in all exposure groups) of the embryos. HPCTP was detected in a main tributary of the Yangtze River Basin. Thus, HPCTP poses a risk to wild fish populations, given the developmental toxicities associated with this chemical and its metabolite.

中文翻译：

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未注册的六苯氧基环三磷腈及其代谢物拮抗视黄酸和视黄酸 X 受体并导致早期发育损伤

六苯氧基环三磷腈 (HPCTP) 是一种未注册的化学品，已在阻燃剂和增塑剂中用作磷酸三苯酯的替代品。在这里，我们在暴露于 HPCTP 的日本青鳉肝脏中鉴定出了其代谢物五苯氧基环三磷腈 (PPCTP)。当性成熟雌性青鳉暴露于 37.0、90.4 和 465.4 ng/L 的 HPCTP 下 35 天时，胚胎中的 HPCTP 浓度（642.1–2531.9 ng/g 脂质重量 [lw]）大大超过了（34.7–298.1 ng/g）。 /g lw）在母体肌肉中，表明母体转移显着。受精后0~9天，胚胎中HPCTP浓度持续下降，而PPCTP浓度上升。HPCTP和PPCTP拮抗视黄酸X受体，50%抑制浓度(IC ₅₀ )分别为34.8和21.2 μM，PPCTP还拮抗视黄酸受体，IC ₅₀为2.79 μM。这种拮抗活动可能导致眼睛畸形（465.4 ng/L 时为 4.7%）、身体畸形（90.4 ng/L 时为 2.1%，465.4 ng/L 时为 6.8%）和早期发育死亡率（所有暴露中为 11.6-21.7%）组）的胚胎。在长江流域的一条主要支流中检测到HPCTP。因此，考虑到与该化学品及其代谢物相关的发育毒性，HPCTP 对野生鱼类种群构成风险。